Shengcai Hou

The Noncoding RNA Expression Profile and the Effect of lncRNA AK126698 on Cisplatin Resistance in Non-Small-Cell Lung Cancer Cell

Background The efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer is limited by the acquired drug resistance. Identification the RNAs related to the cisplatin resistance may help to improve clinical response rates. Methods Microarray expression profiling of mRNAs, lncRNA and miRNA was undertaken in A549 cells and cisplatin resistant A549/CDDP cells. Differentially expressed mRNAs, lncRNAs and miRNAs, verified by realtime RT-PCR, were subjected to pathway analysis. Expression of NKD2 and β-catenin was assessed by realtime RT-PCR and western blot analysis. The effect of lncRNA AK126698 on cisplatin induced apoptosis was investigated by annexin-V/PI flow cytometry. Results In total, 1471 mRNAs, 1380 lncRNAs and 25 miRNAs differentially expressed in A549/CDDP and A549 cells. Among them, 8 mRNAs, 8 lncRNAs and 5 miRNAs differentially expressed in gene chip analysis were validated. High-enrichment pathway analysis identified that some classical pathways participated in proliferation, differentiation, avoidance of apoptosis, and drug metabolism were differently expressed in these cells lines. Gene co-expression network identified many genes like FN1, CTSB, EGFR, and NKD2; lncRNAs including BX648420, ENST00000366408, and AK126698; and miRNAs such as miR-26a and let-7i potentially played a key role in cisplatin resistance. Among which, the canonical Wnt pathway was investigated because it was demonstrated to be targeted by both lncRNAs and miRNAs including lncRNA AK126698. Knockdown lncRNA AK126698 not only greatly decreased NKD2 which can negatively regulate Wnt/β-catenin signaling but also increased the accumulation and nuclear translocation of β-catenin, and significantly depressed apoptosis rate induced by cisplatin in A549 cells. Conclusion Cisplatin resistance in non-small-cell lung cancer cells may relate to the changes in noncoding RNAs. Among these, AK126698 appears to confer cisplatin resistance by targeting the Wnt pathway.

Dysfunction of volume-sensitive chloride channels contributes to cisplatin resistance in human lung adenocarcinoma cells.

Cisplatin-based chemotherapy is the standard therapy used to treat non-small-cell lung cancer. However, its efficacy is largely limited due to the development of drug resistance. The exact mechanism in which cancer cells develop resistance to the drug is not yet fully understood. The purpose of the present study is to test the role of volume-sensitive Cl− channels in cisplatin resistance in human lung adenocarcinoma cells (A549 cells) using patch-clamp recording, cell volume measurement and apoptosis assay. The results showed that cisplatin treatment induced an apoptotic volume decrease (AVD) and activated a Cl− current that showed properties similar to the volume-sensitive outward rectifying (VSOR) Cl− current in wild-type A549 cells. Both the AVD process and VSOR Cl− current were blocked by the chloride channel blocker 4,4′-diisothiocyanostilbene-2,2′ disulfonic acid. However, the A549/CDDP cells, a model of acquired cisplatin resistance cells, on the other hand, had almost no AVD process and VSOR Cl− current when treated with cisplatin. Treatment of A549/CDDP cells with trichostatin A (TSA), a drug that inhibits histone deacetylases, partially restored the VSOR Cl− current and increased cisplatin-induced cell apoptosis rate. These results suggest that impaired activity of VSOR Cl− channels contributes to the cisplatin resistance in A549/CDDP cells.

Silencing of tripartite motif (TRIM) 29 inhibits proliferation and invasion and increases chemosensitivity to cisplatin in human lung squamous cancer NCI‐H520 cells

TRIM29 belongs to the tripartite motif (TRIM) protein family. It has been reported to be a tumor suppressor or have oncogenic function in many cancer types. The aim of this study was to investigate whether downregulation of TRIM29 by small interfering ribonucleic acid (siRNA) could inhibit cell proliferation and invasion and increase chemosensitivity to cisplatin in human lung squamous cancer NCI‐H520 cells in vitro.

Successful extracorporeal membrane oxygenation therapy as a bridge to sequential bilateral lung transplantation for a patient after severe paraquat poisoning

Context. Paraquat is a widely used herbicide that can cause severe to fatal poisoning in humans. The irreversible and rapid progression of pulmonary fibrosis associated with respiratory failure is the main cause of death in the later stages of poisoning. There are infrequent reports of successful lung transplants for cases of severe paraquat poisoning. We expect that this successful case will provide a reference for other patients in similar circumstances. Case details. A 24-year-old female was sent to the hospital approximately 2 hours after ingesting 50 ml of paraquat. She experienced rapidly aggravated pulmonary fibrosis and severe respiratory failure. On the 34th day after ingestion, she underwent intubation and invasive mechanical ventilation. The patient was evaluated for lung transplantation, and veno-venous extracorporeal membrane oxygenation (ECMO) was established as a bridge to lung transplantation on the 44th day. On the 56th day, she successfully underwent a bilateral sequential lung transplantation. Through respiratory and physical rehabilitation and nutrition support, the patient was weaned from mechanical ventilation and extubated on the 66th day. On the 80th day, she was discharged. During the 1-year follow-up, the patient was found to be in good condition, and her pulmonary function improved gradually. Conclusion: We suggest that lung transplantation may be an effective treatment in the end stages of paraquat-induced pulmonary fibrosis and consequential respiratory failure. For patients experiencing a rapid progression to a critical condition in whom lung transplantation cannot be performed immediately (e.g., while awaiting a viable donor or toxicant clearance), ECMO should be a viable bridge to lung transplantation.

Elevated Circulating Levels of Osteopontin Are Associated with Metastasis in Advanced Non-Small Cell Lung Cancer

ObjectiveTo investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer (NSCLC).MethodsThe expression of osteopontin mRNA were detected with RT-PCR technique. The circulating levels of osteopontin were measured through ELASA in 46 NSCLC cases that had not been received any anti-cancer treatment at the time of sampling. The tissues from fifteen patients with benign pulmonary diseases were studied as control group.ResultsThe overall median mRNA expression level of osteopontin was approximately 70-fold higher in tumor tissues than in matched normal lung tissues (P<0.001). Over-expression of osteopontin mRNA was significantly associated with clinical stage (P=0.009). Advanced disease states had higher circulating level of osteopontin (stage I+II versus stage III+VI). In multivariate analysis, stage was the only independent factor influencing circulating levels of osteopontin. All patients were followed up for 12 months, 2 of the 46 patients with both osteopontin mRNA expression and elevated plasma osteopontin levels had local recurrence and 10 had distant metastasis. There was a significant difference in the osteopontin levels between metastasis group and non-metastasis group.ConclusionPreoperative plasma levels of osteopontin are significantly associated with post-operative metastasis in advanced NSCLC.

Abnormal bone mineral density and bone turnover marker expression profiles in patients with primary spontaneous pneumothorax.

BACKGROUND To examine the bone mineral density (BMD) and the role of bone biomarkers, including bone formation marker procollagen type I aminoterminal propeptide (PINP) and N-terminal midmolecule fragment osteocalcin (N-MID), bone resorption marker b-C-telopeptides of type I collagen (b-CTX) and tartrate-resistant acid phosphatase 5b (TRACP5b) in the pathogenesis of PSP. METHODS Eighty-three consecutive primary spontaneous pneumothorax (PSP) patients (PSP group) and 87 healthy individuals (control group) were enrolled in this study. General data, including gender, age, height, weight, and body mass index (BMI), were recorded. Dual-energy X-ray absorptiometry, electrochemiluminescence immunoassay (ECLIA), and ELISA were used to evaluate bone mineral density and expression levels of bone metabolism markers, including PINP, b-CTX, TRACP5b, N-MID, and 25-hydroxyvitamin D (25-OH VD). RESULTS Mean height was significantly greater in the PSP group compared with the control group, whereas weight and BMI were lower. Patients in the PSP group had significantly lower average bone mineral density, which mainly manifested as osteopenia (11/12, 91.7%); however, only one patient (8.3%) developed osteoporosis. Serum overexpression of PINP, b-CTX, TRACP5b, and N-MID were found in PSP patients. Expression of 25-OH VD was low in PSP patients. Bone resorption markers showed positive linear relationships with bone formation markers in all participants; whereas only TRACP5b expression negatively correlated with 25-OH VD. Expression levels of all bone turnover markers negatively correlated with BMI. Regression analysis identified risk factors of PSP as age, height, weight, and TRACP5b and 25-OH VD expression levels; whereas gender and PINP, b-CTX, and N-MID expression levels were not significantly associated with the onset of PSP. CONCLUSIONS It had lower bone mineral density in PSP patients. Bone formation marker PINP, N-MID and bone resorption marker b-CTX, TRACP5b were upregulated in PSP patients. 25-OH VD expression was relatively low in this population of PSP patients. Age, height, weight, and expression levels of TRACP5b and 25-OH VD may be risk factors for PSP.

Application of Extracorporeal Membrane Oxygenation in Giant Bullae Resection

A patient with chronic obstructive pulmonary disease and lung bullae was admitted to our hospital. He suffered respiratory failure and was given mechanical ventilation. However, the bullae became more and more large and compressed the lungs on both sides. We managed extracorporeal membrane oxygenation (ECMO) to maintain the patients blood oxygenation, and performed bullae resection surgery successfully. The patients pulmonary function recovered gradually after the operation and he returned home. In our experience with this case, ECMO can be used in bullae resection.

Esophagogastric reconstruction using remnant stomach with a single vessel pedicel: Technique and outcomes

Esophageal cancer with a history of distal gastrectomy is a clinical problem. To our knowledge there have been no reports of remnant stomach fed from the left gastroepiploic artery being used in esophageal reconstruction. We, herein, report four cases of esophagogastric reconstruction using remnant stomach with a single left gastroepiploic vascular pedicel. It is more functional to use the remnant stomach than other replacements. Meanwhile, the gastric conduit fed from the left gastroepiploic artery showed sufficient vascularity and stable gastroesophageal anastomosis. The technique and outcomes in follow‐up have proven feasible and save time.

Mediastinal small-cell lung carcinoma after right lung transplant for pulmonary interstitial fibrosis.

Pulmonary carcinoma is uncommon after lung transplant, but doubtlessly affects recipient survival independently of other complications. Small cell lung cancer is much rarer after transplant than non-small cell lung cancer. We report a case of mediastinal small cell lung carcinoma confirmed by endobronchial ultrasound biopsy that occurred 18 months after a single lung transplant for interstitial pulmonary fibrosis in a 58-year-old male nonsmoker. The patient died shortly after of distant metastasis. Our report confirms the usefulness of tumor markers and positron-emission tomography-computed tomography as routine tests for earlier detection of malignant disease after lung transplant.

Erratum to the significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for predicting venous thromboembolism: a prospective, single center study

Background The high incidence of venous thromboembolism (VTE) has been perceived in post thoracic surgery patients. However, the significance of perioperative coagulation and fibrinolysis related parameters after lung surgery for VTE predicting is not clear. To investigate that, we conducted a prospective single center study. Methods A total of 111 patients undergoing lung surgery were enrolled in this study, included 52 primary lung cancer patients and 59 benign lung disease patients from July 2016 to March 2017. Preoperative and postoperative days 1, 3, and 5 coagulation and fibrinolysis related parameters were tested, including antithrombin (AT), fibrinogen degradation product (FDP), prothrombin time (PT), prothrombin time activity (PA), prothrombin time ratio (PR), international normalized ratio (INR), activated partial thromboplastin time (APTT), plasma fibrinogen (FBG), thrombin time (TT) and D-Dimer. The Doppler ultrasonography was performed before and after surgery for deep venous thrombosis (DVT) confirmation. Patients with new postoperative DVT, unexplained dyspnea, hemoptysis, chest pain, or high Caprini score (≥9) were received further computer tomography pulmonary angiography (CTPA) for pulmonary embolism (PE). We used the area under receiver-operating-characteristic (ROC) curve to discriminate patients between those who developed VTE and those who did not. Single factor analysis was utilized to define risk factors associated with VTE. Results The overall incidence of VTE was 16.2% (18/111). The incidence of VTE in primary lung cancer patients was 23.1% (12/52), much higher than that in benign lung diseases 10.2% (6/59), but did not reach statistical significance (P=0.066). Among 18 VTE patients, 83.3% was DVT, 16.7% was DVT + PE and 72.2% was muscular veins of the calf thrombosis. D-Dimer was much higher in VTE group than that in non-VTE group preoperatively and at postoperative days 1, 3 (0.64±0.24 vs. 0.33±0.06, P=0.007; 3.14±0.75 vs. 1.51±0.09, P=0.005, and 1.88±0.53 vs. 0.76±0.05, P=0.001, respectively). And the ROC curve areas of preoperative and postoperative days 1, 3 of D-Dimer were 0.70, 0.71 and 0.74, respectively. And FDP was much higher in VTE group than that in non-VTE group at postoperative day 3 (6.78±1.43 vs. 3.79±0.15, P=0.004). But AT, PT, PA, PR, INR, APTT, FBG and TT there were no significantly difference. Conclusions The overall incidence of VTE after lung surgery was 16.2%. The patients with preoperative high D-Dimer should receive VTE prophylaxis.